Efforts to maximize the benefits and minimize the risks associated with drugs continue to be impeded by suboptimal prescribing, inadequate monitoring of patients'outcomes, and inadequate prescriber education and support to overcome these limitations. As a result, the US healthcare system suffers from persistent problems of underuse, overuse and misuse of drugs, with unacceptably high rates of preventable errors, adverse effects and suboptimal patient health outcomes. To address these problems, we propose a CERT organized around the following theme: Tools for Optimizing Prescribing, Monitoring and Education (TOP-MED). The long term objective of our CERT is to improve the safety, efficacy and cost-effectiveness of drug therapy by increasing the appropriateness of prescribing and the quality of monitoring. The short term objective is to develop, redesign, refine, integrate, test, deploy and disseminate tools and training materials in five key areas: drug formularies, drug utilization review, lab-pharmacy linkages, N-of-1 trials and pharmacoeconomics. To achieve these objectives, the TOP-MED CERT will pursue the following specific aims: 1. Revitalize the drug formulary as an evidenced based tool for directing drug therapy decisions. 2. Re-engineer drug usage review (DUR) systems and processes so that data analysis is easier, more timely and more likely to yield valid generalizations. 3. Reduce prescribing errors and enhance recognition of adverse drug effects in high hazard contexts by linking lab and pharmacy information systems and generating clinical alerts when problems are detected. 4. Develop, deploy and evaluate an N-of-1 trial service, integrated into a formulary restriction program, in order to support the goal of individualized therapy without succumbing to the unsafe, unscientific experimentation that is often now the norm. 5. Implement and study the impact of pharmacoeconomic support to enhance formulary decision making, as well as evaluate the cost-effectiveness of other interventions. Cutting across these five aims will be initiatives to disseminate and deploy these tools in a more rigorous and far-reaching fashion;to provide support to make the tools easier to use;to enhance the buy-in, motivation and enthusiasm of prescribers to use the tools;to link the tools with each other in order to gain greater synergies, and to share the knowledge gained and lessons learned across multiple institutions. Headquartered at the University of Illinois at Chicago (UIC), and leveraging collaborations with the Cook County Bureau of Health Services, Northwestern Memorial Hospital, University of Washington, the VA Center for Medication Safety, Advocate Health Care, the Illinois Hospital Association and the Illinois Department of Public Health, the TOPMED CERT will be able to focus on the needs of multiple AHRQ priority populations.